tbuckley/cabot-search huggingface dataset:
A foundational vision transformer improves diagnostic performance for electrocardiograms
Authors: Akhil Vaid, Joy Jiang, Ashwin Sawant, Stamatios Lerakis, Edgar Argulian, Yuri Ahuja, Joshua Lampert, Alexander Charney, Hayit Greenspan, Jagat Narula, Benjamin Glicksberg, Girish N Nadkarni
Journal: npj Digital Medicine (2023)

Abstract The electrocardiogram (ECG) is a ubiquitous diagnostic modality. Convolutional neural networks (CNNs) applied towards ECG analysis require large sample sizes, and transfer learning approaches for biomedical problems may result in suboptimal performance when pre-training is done on natural images. We leveraged masked image modeling to create a vision-based transformer model, HeartBEiT, for electrocardiogram waveform analysis. We pre-trained this model on 8.5 million ECGs and then compared performance vs. standard CNN architectures for diagnosis of hypertrophic cardiomyopathy, low left ventricular ejection fraction and ST elevation myocardial infarction using differing training sample sizes and independent validation datasets. We find that HeartBEiT has significantly higher performance at lower sample sizes compared to other models. We also find that HeartBEiT improves explainability of diagnosis by highlighting biologically relevant regions of the EKG vs. standard CNNs. Domain specific pre-trained transformer models may exceed the classification performance of models trained on natural images especially in very low data regimes. The combination of the architecture and such pre-training allows for more accurate, granular explainability of model predictions.
Emergence of Malignant T-Cell Intraclonal <i>CDR3</i> Variants in Mycosis Fungoides
Authors: Laura Gleason, Alexa Cohen, Andrew P. South, Pierluigi Porcu, Neda Nikbakht
Journal: JAMA Dermatology (2023)

This case report describes 3 patients with mycosis fungoides with CDR3 variants.
Nicotine exacerbates atherosclerosis and plaque instability via NLRP3 inflammasome activation in vascular smooth muscle cells
Authors: Junqing An, Liu Ouyang, Changjiang Yu, Sean Michael Carr, Tharmarajan Ramprasath, Zhixue Liu, Ping Song, Ming-Hui Zou, Ye Ding
Journal: Theranostics (2023)

Rationale: Nicotine has been reported to be a strong risk factor for atherosclerosis.However, the underlying mechanism by which nicotine controls atherosclerotic plaque stability remain largely unknown.Objective: The aim of this study was to evaluate the impact of lysosomal dysfunction mediated NLRP3 inflammasome activation in vascular smooth muscle cell (VSMC) on atherosclerotic plaque formation and stability in advanced atherosclerosis at the brachiocephalic arteries (BA).Methods and Results: Features of atherosclerotic plaque stability and the markers for NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome were monitored in the BA from nicotine or vehicle-treated apolipoprotein E deficient (Apoe -/ -) mice fed with Western-type diet (WD).Nicotine treatment for 6 weeks accelerated atherosclerotic plaque formation and enhanced the hallmarks of plaque instability in BA of Apoe -/ - mice.Moreover, nicotine elevated interleukin 1 beta (IL-1β) in serum and aorta and was preferred to activate NLRP3 inflammasome in aortic vascular smooth muscle cells (VSMC).Importantly, pharmacological inhibition of Caspase1, a key downstream target of NLRP3 inflammasome complex, and genetic inactivation of NLRP3 significantly restrained nicotine-elevated IL-1β in serum and aorta, as well as nicotine-stimulated atherosclerotic plaque formation and plaque destabilization in BA.We further confirmed the role of VSMC-derived NLRP3 inflammasome in nicotine-induced plaque instability by using VSMC specific TXNIP (upstream regulator of NLRP3 inflammasome) deletion mice.Mechanistic study further showed that nicotine induced lysosomal dysfunction resulted in cathepsin B cytoplasmic release.Inhibition or knockdown of cathepsin B blocked nicotine-dependent inflammasome activation.Conclusions: Nicotine promotes atherosclerotic plaque instability by lysosomal dysfunction-mediated NLRP3 inflammasome activation in vascular smooth muscle cells.
M2 isoform of pyruvate kinase rewires glucose metabolism during radiation therapy to promote an antioxidant response and glioblastoma radioresistance
Authors: Justine Bailleul, Yangjingyi Ruan, Lobna Abdulrahman, Andrew J Scott, Taha Yazal, David Sung, Keunseok Park, Hanna Hoang, Juan Nathaniel, Fang-I Chu, Daisy Palomera, Anahita Sehgal, Jonathan E Tsang, David A Nathanson, Shili Xu, Junyoung O Park, Johanna ten Hoeve, Kruttika Bhat, Nathan Qi, Harley I Kornblum, Dorthe Schaue, William H McBride, Costas A Lyssiotis, Daniel R Wahl, Erina Vlashi
Journal: Neuro-Oncology (2023)

Abstract Background Resistance to existing therapies is a significant challenge in improving outcomes for glioblastoma (GBM) patients. Metabolic plasticity has emerged as an important contributor to therapy resistance, including radiation therapy (RT). Here, we investigated how GBM cells reprogram their glucose metabolism in response to RT to promote radiation resistance. Methods Effects of radiation on glucose metabolism of human GBM specimens were examined in vitro and in vivo with the use of metabolic and enzymatic assays, targeted metabolomics, and FDG-PET. Radiosensitization potential of interfering with M2 isoform of pyruvate kinase (PKM2) activity was tested via gliomasphere formation assays and in vivo human GBM models. Results Here, we show that RT induces increased glucose utilization by GBM cells, and this is accompanied with translocation of GLUT3 transporters to the cell membrane. Irradiated GBM cells route glucose carbons through the pentose phosphate pathway (PPP) to harness the antioxidant power of the PPP and support survival after radiation. This response is regulated in part by the PKM2. Activators of PKM2 can antagonize the radiation-induced rewiring of glucose metabolism and radiosensitize GBM cells in vitro and in vivo. Conclusions These findings open the possibility that interventions designed to target cancer-specific regulators of metabolic plasticity, such as PKM2, rather than specific metabolic pathways, have the potential to improve the radiotherapeutic outcomes in GBM patients.
PCSK9 attenuates efferocytosis in endothelial cells and promotes vascular aging
Authors: Shijie Liu, Jinzi Wu, Amanda Stolarz, Huiliang Zhang, Marjan Boerma, Stephanie D. Byrum, Nancy J Rusch, Zufeng Ding
Journal: Theranostics (2023)

Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that binds to low-density lipoprotein receptors.Efferocytosis is the process by which phagocytes remove apoptotic cells.Both PCSK9 and efferocytosis play important roles in regulating redox biology and inflammation, the key factors contributing to vascular aging.This study was designed to investigate the impact of PCSK9 on efferocytosis in endothelial cells (ECs) and its implications in vascular aging.Methods and Results: Studies were performed in primary human aortic ECs (HAECs) and primary mouse aortic ECs (MAECs) isolated from male wild-type (WT) and PCSK9 -/-mice, and in young and aged mice treated with saline or the PCSK9 inhibitor Pep2-8.Our findings include that recombinant PCSK9 protein induces defective efferocytosis and aging marker senescence-associated-β-galactosidase (SA-β-gal) expression in ECs, while PCSK9 -/-restores efferocytosis and inhibits SA-β-gal activity.Further studies in aged mice showed that endothelial deficiency of MerTK, a critical receptor for efferocytosis that allows phagocytes to detect the presence of apoptotic cells, may be an indicator of vascular dysfunction in the aortic arch.Pep2-8 treatment markedly restored efferocytosis in endothelium from the aged mice.A proteomics study in the aortic arch from aged mice revealed that Pep2-8 administration significantly downregulates expression of NOX4, MAPK subunits, NF-κB, and secretion of pro-inflammatory cytokines, all known to promote vascular aging.Immunofluorescent staining showed that Pep2-8 administration upregulates expression of eNOS and downregulates expression of pro-IL-1β, NF-κB and p22 phox compared to saline treated group.Conclusions: These findings provide initial evidence for the ability of aortic ECs to accomplish efferocytosis and argue for a role of PCSK9 in attenuating EC efferocytosis, thereby leading to vascular dysfunction and acceleration in vascular aging.
No Difference in Quality, Cost for Patients Treated by Hospitalist MDs vs DOs
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Interventions to improve outcomes for caregivers of patients with advanced cancer: a meta-analysis
Authors: Ronald Chow, Jean J Mathews, Emily YiQin Cheng, Samantha Lo, Joanne Wong, Sorayya Alam, Breffni Hannon, Gary Rodin, Rinat Nissim, Sarah Hales, Dio Kavalieratos, Kieran L Quinn, George Tomlinson, Camilla Zimmermann
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Family caregivers of patients with advanced cancer often have poor quality of life (QOL) and mental health. We examined the effectiveness of interventions offering support for caregivers of patients with advanced cancer on caregiver QOL and mental health outcomes. Methods We searched Ovid MEDLINE, EMBASE, Cochrane CENTRAL, and Cumulative Index to Nursing and Allied Health Literature databases from inception through June 2021. Eligible studies reported on randomized controlled trials for adult caregivers of adult patients with advanced cancer. Meta-analysis was conducted for primary outcomes of QOL, physical well-being, mental well-being, anxiety, and depression, from baseline to follow-up of 1-3 months; secondary endpoints were these outcomes at 4-6 months and additional caregiver burden, self-efficacy, family functioning, and bereavement outcomes. Random effects models were used to generate summary standardized mean differences (SMD). Results Of 12 193 references identified, 56 articles reporting on 49 trials involving 8554 caregivers were eligible for analysis; 16 (33%) targeted caregivers, 19 (39%) patient–caregiver dyads, and 14 (29%) patients and their families. At 1- to 3-month follow-up, interventions had a statistically significant effect on overall QOL (SMD = 0.24, 95% confidence interval [CI] = 0.10 to 0.39); I2 = 52.0%), mental well-being (SMD = 0.14, 95% CI = 0.02 to 0.25; I2 = 0.0%), anxiety (SMD = 0.27, 95% CI = 0.06 to 0.49; I2 = 74.0%), and depression (SMD = 0.34, 95% CI = 0.16 to 0.52; I2 = 64.4) compared with standard care. In narrative synthesis, interventions demonstrated improvements in caregiver self-efficacy and grief. Conclusions Interventions targeting caregivers, dyads, or patients and families led to improvements in caregiver QOL and mental health. These data support the routine provision of interventions to improve well-being in caregivers of patients with advanced cancer.
NOX4 is a potential therapeutic target in septic acute kidney injury by inhibiting mitochondrial dysfunction and inflammation
Authors: Jiameng Li, Liya Wang, Bo Wang, Zhuyun Zhang, Luojia Jiang, Zheng Qin, Yuliang Zhao, Baihai Su
Journal: Theranostics (2023)

Rationale: Sepsis is a severe clinical syndrome featured through organ dysfunction due to infection, while the accompanying acute kidney injury (AKI) is linked to significant incidence of morbidity as well as mortality. Recently, emerging evidence has revealed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is implicated in various renal diseases, while its role and modulation in septic acute kidney injury (S-AKI) remains largely unknown. Methods:In vivo, S-AKI in wild-type and renal tubular epithelial cell (RTEC)-specific NOX4 knockout mice was induced by lipopolysaccharides (LPS) injection or cecal ligation and puncture (CLP). In vitro, TCMK-1 (mouse kidney tubular epithelium cell line) cells were treated with LPS. Serum and supernatant biochemical, mitochondrial dysfunctional, inflammatory and apoptotic parameters were measured and compared across groups. The activation of reactive oxygen species (ROS) and NF-κB signaling was also assessed. Results: NOX4 was predominantly upregulated in RTECs of S-AKI mouse model induced by LPS/CLP and cultured TCMK-1 cells exposed to LPS. RTEC-specific deletion of NOX4 or pharmacological inhibition of NOX4 by GKT137831 both alleviated LPS/CLP-injured renal function and pathology in mice. Furthermore, NOX4 inhibition alleviated mitochondrial dysfunction supported by ultrastructural damage, reduction of ATP production and mitochondrial dynamics imbalance, together with inflammation and apoptosis in kidney injured by LPS/CLP and TCMK-1 cells injured by LPS, while NOX4 overexpression aggravated the above-mentioned indices in TCMK-1 cells with LPS stimulation. Mechanism-wise, the raised NOX4 in RTECs may induce ROS and NF-κB signaling activation in S-AKI. Conclusions: Collectively, genetic or pharmacological inhibition of NOX4 protects from S-AKI by reducing generation of ROS and activation of NF-κB signal, which suppress mitochondrial dysfunction, inflammation together with apoptosis. NOX4 may act as a novel target for the S-AKI therapy.
A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression Among University Students
Authors: Corina Benjet, Nur Hani Zainal, Yesica Albor, Libia Alvis-Barranco, Nayib Carrasco-Tapias, Carlos C. Contreras-Ibáñez, Lorena Cudris-Torres, Francisco R. de la Peña, Noé González, José Benjamín Guerrero-López, Raúl A. Gutierrez-Garcia, Ana Lucía Jiménez-Peréz, Maria Elena Medina-Mora, Pamela Patiño, Pim Cuijpers, Sarah M. Gildea, Alan E. Kazdin, Chris J. Kennedy, Alex Luedtke, Nancy A. Sampson, Maria V. Petukhova, Ronald C. Kessler
Journal: JAMA Psychiatry (2023)

Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT.
Outcomes in Patients with High-Risk Features after Fixed-Duration Ibrutinib plus Venetoclax: Phase II CAPTIVATE Study in First-Line Chronic Lymphocytic Leukemia
Authors: John N. Allan, Ian W. Flinn, Tanya Siddiqi, Paolo Ghia, Constantine S. Tam, Thomas J. Kipps, Paul M. Barr, Anna Elinder Camburn, Alessandra Tedeschi, Xavier C. Badoux, Ryan Jacobs, Bryone J. Kuss, Livio Trentin, Cathy Zhou, Anita Szoke, Christopher Abbazio, William G. Wierda
Journal: Clinical Cancer Research (2023)

The CAPTIVATE study investigated first-line ibrutinib plus venetoclax for chronic lymphocytic leukemia in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). We report outcomes of fixed-duration ibrutinib plus venetoclax in patients with high-risk genomic features [del(17p), TP53 mutation, and/or unmutated immunoglobulin heavy chain (IGHV)] in CAPTIVATE.
EPIC-0307-mediated selective disruption of PRADX–EZH2 interaction and enhancement of temozolomide sensitivity to glioblastoma via inhibiting DNA repair and MGMT
Authors: Lei Xin, Yanli Tan, Yuanxue Zhu, Xiaoteng Cui, Qixue Wang, Jixing Zhao, Shaohui Tian, Can Xu, Menglin Xiao, Biao Hong, Jianglong Xu, Xiaoye Yuan, Changsheng Wang, Chunsheng Kang, Chuan Fang
Journal: Neuro-Oncology (2023)

Abstract Background Temozolomide (TMZ) treatment efficacy in glioblastoma (GBM) has been limited by resistance. The level of O-6-methylguanine-DNA methyltransferase (MGMT) and intrinsic DNA damage repair factors are important for the TMZ response in patients. Here, we reported a novel compound, called EPIC-0307, that increased TMZ sensitivity by inhibiting specific DNA damage repair proteins and MGMT expression. Methods EPIC-0307 was derived by molecular docking screening. RNA immunoprecipitation (RIP), and chromatin immunoprecipitation by RNA (ChIRP) assays were used to verify the blocking effect. Chromatin immunoprecipitation (ChIP) and co-immunoprecipitation (Co-IP) assays were performed to explore the mechanism of EPIC-0307. A series of in vivo and in vitro experiments were designed to evaluate the efficacy of EPIC-0307 in sensitizing GBM cells to TMZ. Results EPIC-0307 selectively disrupted the binding of PRADX to EZH2 and upregulated the expression of P21 and PUMA, leading to cell cycle arrest and apoptosis in GBM cells. EPIC-0307 exhibited a synergistic inhibitory effect on GBM when combined with TMZ by downregulating TMZ-induced DNA damage repair responses and epigenetically silencing MGMT expression through modulating the recruitment of ATF3-pSTAT3-HDAC1 regulatory complex to the MGMT promoter. EPIC-0307 demonstrated significant efficacy in suppressing the tumorigenesis of GBM cells, restoring TMZ sensitivity. Conclusion This study identified a potential small-molecule inhibitor (SMI) EPIC-0307 that selectively disrupted the PRADX–EZH2 interaction to upregulate expressions of tumor suppressor genes, thereby exerting its antitumor effects on GBM cells. EPIC-0307 treatment also increased the chemotherapeutic efficacy of TMZ by epigenetically downregulating DNA repair-associate genes and MGMT expression in GBM cells.
Construction of intelligent moving micro/nanomotors and their applications in biosensing and disease treatment
Authors: Yingshu Guo, Dan Jing, Shiwei Liu, Quan Yuan
Journal: Theranostics (2023)

Micro/nanomotors are containers that pass through liquid media and carry cargo.Because they are tiny, micro/nanomotors exhibit excellent potential for biosensing and disease treatment applications.However, their size also makes overcoming random Brownian forces very challenging for micro/nanomotors moving on targets.Additionally, to achieve desired practical applications, the expensive materials, short lifetimes, poor biocompatibility, complex preparation methods, and side effects of micro/nanomotors must be addressed, and potential adverse effects must be evaluated both in vivo and in practical applications.This has led to the continuous development of key materials for driving micro/nanomotors.In this work, we review the working principles of micro/nanomotors.Metallic and nonmetallic nanocomplexes, enzymes, and living cells are explored as key materials for driving micro/nanomotors.We also consider the effects of exogenous stimulations and endogenous substance conditions on micro/nanomotor motions.The discussion focuses on micro/nanomotor applications in biosensing, treating cancer and gynecological diseases, and assisted fertilization.By addressing micro/nanomotor shortcomings, we propose directions for further developing and applying micro/nanomotors.
Myofiber Baf60c controls muscle regeneration by modulating Dkk3-mediated paracrine signaling
Authors: Jingya Xu, Xiaofei Li, Wei Chen, Ziyin Zhang, Yanping Zhou, Yahui Gou, Cheng-an Lv, Lu Jin, Xinyuan Qiu, Shengshan Ma, Qing-Qian Wu, Tongyu Liu, Lin Mi, Zhuoying Yang, Ting Yu, Xiaowen Pan, Yu Feng, Pengfei Shan, Zhuo-Xian Meng
Journal: The Journal of Experimental Medicine (2023)

Obesity and type 2 diabetes (T2D) are the leading causes of the progressive decline in muscle regeneration and fitness in adults. The muscle microenvironment is known to play a key role in controlling muscle stem cell regenerative capacity, yet the underlying mechanism remains elusive. Here, we found that Baf60c expression in skeletal muscle is significantly downregulated in obese and T2D mice and humans. Myofiber-specific ablation of Baf60c in mice impairs muscle regeneration and contraction, accompanied by a robust upregulation of Dkk3, a muscle-enriched secreted protein. Dkk3 inhibits muscle stem cell differentiation and attenuates muscle regeneration in vivo. Conversely, Dkk3 blockade by myofiber-specific Baf60c transgene promotes muscle regeneration and contraction. Baf60c interacts with Six4 to synergistically suppress myocyte Dkk3 expression. While muscle expression and circulation levels of Dkk3 are markedly elevated in obese mice and humans, Dkk3 knockdown improves muscle regeneration in obese mice. This work defines Baf60c in myofiber as a critical regulator of muscle regeneration through Dkk3-mediated paracrine signaling.
Elevated nuclear PIGL disrupts the cMyc/BRD4 axis and improves PD-1 blockade therapy by dampening tumor immune evasion
Authors: Hua Yu, Tiezhu Shi, Linli Yao, Dongwei Xu, Yufeng Ding, Qiang Xia, Wei Liu, Xiongjun Wang
Journal: Cellular and Molecular Immunology (2023)
Carolina Blues
Authors: Andrew M. Fine, Laura C. Fine, Thomas Pranikoff
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal